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Due to the unique structural, electronic and electrochemical features, the macrocyclic complexes are recognized as potential models in diverse field of research like electrocatalysis, biological, pharmaceuticals etc. Herein, we prepared MIIN4-macrocyclic complexes (M = FeII and CoII) via condensation of 2,3-diaminopyridine and 2,6-pyridinedicarboxylic acid in presence of metal salts. These synthesized complexes were characterized using multiple spectroscopies. The octahedral geometry was assigned to the complexes on the basis of electronic spectral studies. Further, the electrochemical behavior of these complexes was evaluated using cyclic voltammetry, and the results agreed with the stability of uncommon oxidation states of the corresponding transition metal ion. These fundamental studies will help to concern community to design the efficient macrocyclic models for various applications. [ABSTRACT FROM AUTHOR]

An Erratum to this paper has been published: https://doi.org/10.1134/S1068162023330014 [ABSTRACT FROM AUTHOR]

Greener and sustainable synthetic strategies have been evolving as the demanding domain of organic synthesis during the last decade. Green synthesis involves the development of method that decrease or eliminate the use of hazardous chemicals, and make use of renewable or recyclable resources. By incorporating the fundamentals and methodologies of green synthesis, organic chemists have the ability to develop valuable organic molecular frameworks which also demonstrate a strong commitment to environmental sustainability. In this context, the nanoparticle has garnered significant interest due to its various features, adhering to the principles of green synthesis. Specifically, magnetic nanoparticles have been trending extensive uses in green synthesis throughout the past decade. The role of magnetic nanoparticle has an irreplaceable place in the synthesis of biologically valuable frameworks named as quinoline. Quinoline are considered a privileged structure among organic compounds and offer a promising avenue for identifying lead structures in the search of new synthetic molecules (Saquinavir, Imiquimod and Reabamipide) having potential medicinal values and other important prospects. So, it's always indeed to the organic and medicinal chemist to develop biologically active frameworks by the green synthesis. The current manuscript consolidates the existing research on properties of environment-friendly magnetic nanoparticles for generating an extended range of valuable quinoline derivatives., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: First classified in 2016, high-grade B-cell lymphoma (HGBCL) is a lymphoid neoplasm that is typically seen as an aggressive lymphoproliferative disorder (LPD). In most patients with HGBCL, various oncogene rearrangements present with advanced clinical features, such as central nervous system involvement. Patients with underlying autoimmune and rheumatologic conditions, such as rheumatoid arthritis, are at higher risk for developing LPDs, including highly aggressive subtypes of non-Hodgkin lymphomas such as HGBCL., Case Presentation: We present a case of stage IV double-hit HGBCL with the presence of MYC and BCL6 gene rearrangements in an older veteran with rheumatoid arthritis treated with methotrexate. An excellent sustained response was observed for the patient's disease within 4 weeks of methotrexate discontinuation. To our knowledge, this is the first reported response to methotrexate discontinuation for a patient with HGBCL., Conclusions: Reducing immunosuppression should be considered in all patients with LPDs associated with autoimmune conditions or immunosuppressive medications, regardless of additional multiagent systemic therapy administration., Competing Interests: Author disclosures: The authors report no actual or potential conflicts of interest or outside soruces of funding with regard to this article., (Copyright © 2024 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Background: Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of several solid tumors. The use of ICIs is expected to rise as a growing number of indications are approved for their use by the US Food and Drug Administration and with the increasing number of patients with cancer. Unfortunately, ICIs are associated with the development of immune-mediated adverse reactions (IMARs). About 5% to 10% of patients developing severe toxicities requiring treatment postponement or discontinuation. IMARs can affect any organ, but most frequently the skin and endocrine glands are involved., Case Presentation: We present a case series of IMARs observed at the New Mexico Veterans Affairs Medical Center. First, we present a case of grade 4 myocarditis in an 84-year-old man receiving chemoimmunotherapy for lung adenocarcinoma to demonstrate the rapid progression of this rare condition. Second, we present a case of uveitis in a 70-year-old man with superficial bladder cancer undergoing treatment with pembrolizumab. Finally, we present a case of a 63-year-old man with pleuritis and organizing pneumonia secondary to dual ICI treatment (nivolumab and ipilimumab) for mesothelioma. A discussion regarding the epidemiology of these IMARs, expected course, and optimal management follows each rare toxicity described., Conclusions: Though these toxicities are uncommon, they serve as a reminder to clinicians across specialties that IMARs can drive the acute deterioration of any organ, and consideration of toxicities secondary to ICIs should be considered for any atypical presentation of unclear etiology., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article., (Copyright © 2023 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Purpose: Neurotrophic tyrosine receptor kinase 1-3 ( NTRK1-3 ) gene fusions are found in a broad range of tumor types. Clinical trials demonstrated high response rates to tropomyosin receptor kinase (TRK) inhibitors in NTRK fusion-positive cancers, but few reports have described real-world experience with these targeted agents. We evaluated the prevalence of NTRK fusions and the outcomes with TRK inhibitor therapy in a real-world population of patients in the Veterans Health Administration., Methods: Patients with NTRK fusions or rearrangements were identified from the Veterans Affairs (VA) National Precision Oncology Program (NPOP), and patients who were prescribed TRK inhibitors were identified from the Corporate Data Warehouse. Baseline data and clinical outcomes were obtained by retrospective review of medical records., Results: A total of 33 patients with NTRK fusions or rearrangements were identified, including 25 patients comprising 0.12% of all patients with solid tumors sequenced through VA NPOP. Twelve patients with NTRK fusions or rearrangements were treated with TRK inhibitors, none of whom had objective responses. Eight patients experienced toxicities leading to drug interruption, dose reduction, or discontinuation., Conclusion: In this retrospective study of VA patients, NTRK fusions and rearrangements were less common than in previous studies, and objective responses to TRK inhibitors were not observed. Real-world experience with TRK inhibitors differs markedly from clinical trial findings, possibly due to differences in patient demographics, tumor types, and sequencing methods. Our findings highlight the need to study TRK inhibitors in the real-world setting and in populations underrepresented in clinical trials.

Background: Until recently, multi-agent chemotherapy (CT) was the standard of care for patients with advanced non-small cell lung cancer (NSCLC). Clinical trials have confirmed benefits in overall survival (OS) and progression-free survival with immunotherapy (IO) compared to CT. This study compares real-world treatment patterns and outcomes between CT and IO administrations in second-line (2L) settings for patients with stage IV NSCLC., Materials and Methods: This retrospective study included patients in the United States Department of Veterans Affairs healthcare system diagnosed with stage IV NSCLC during 2012-2017 and receiving IO or CT in the 2L. Patient demographics and clinical characteristics, healthcare resource utilization (HCRU), and adverse events (AEs) were compared between treatment groups. Logistic regression was used to examine differences in baseline characteristics between groups, and inverse probability weighting multivariable Cox proportional hazard regression was used to analyze OS., Results: Among 4,609 Veterans who received first-line (1L) therapy for stage IV NSCLC, 96% received 1L CT alone. A total of 1,630 (35%) were administered 2L systemic therapy, with 695 (43%) receiving IO and 935 (57%) receiving CT. Median age was 67 years (IO group) and 65 years (CT group); most patients were male (97%) and white (76-77%). Patients administered 2L IO had a higher Charlson Comorbidity Index than those administered CT (p = 0.0002). 2L IO was associated with significantly longer OS compared with CT (hazard ratio 0.84, 95% CI 0.75-0.94). IO was more frequently prescribed during the study period (p < 0.0001). No difference in rate of hospitalizations was observed between the two groups., Conclusions: Overall, the proportion of advanced NSCLC patients receiving 2L systemic therapy is low. Among patients treated with 1L CT and without IO contraindications, 2L IO should be considered, as this supports potential benefit of IO for advanced NSCLC. The increasing availability and indications for IO will likely increase the administration of 2L therapy to NSCLC patients., Competing Interests: This study was supported by Bristol-Myers Squibb Company (BMS). Dr. Allo was affiliated with BMS. BMS did not have access to underlying data and did not contribute to any data analysis. This commercial affiliation does not alter the adherence to PLOS ONE policies on sharing data and materials. The authors declare no other competing interests., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality in India. To clarify rates of actionable mutations, and thereby identify opportunities to improve the delivery of best available care for a large volume of patients, a comprehensive review of available data is warranted., Methods: Studies that reported prevalence of any actionable gene variant among adult Indian patients with advanced NSCLC were selected from three databases (PubMed, EMBASE, and Cochrane Library). Ranges in actionable variant prevalence were reported. Meta-analysis of proportions was completed among studies specifically evaluating mutational prevalence within ALK or EGFR. Sensitivity analyses were undertaken among populations sharing high heterogeneity., Results: Twenty-six studies were selected. Ranges in actionable mutational prevalence among NSCLC patients were as follows: ALK: 4.1-21.4%, BRAF: 1.5-3.5%, EGFR: 11.9-51.8%, HER2: 0-1.5%, KRAS: 4.5-6.4%, NTRK: 0-.7%, and ROS-1: 3.5-4.1%. Following sensitivity analysis, pooled ALK mutational prevalence rates were 8.3% (95% CIs: 6.6-10.4%) and 4.01% (95% CIs: 2.3-7.0) for adenocarcinoma and NSCLC patients, respectively. Pooled EGFR mutational prevalence rates were 28.7% (95% CIs: 23.5-34.6%) and 24.2% (95% CIs: 19.9-29.1%) for adenocarcinoma and NSCLC patients, respectively., Conclusions: Nearly 40% of Indian patients with advanced adenocarcinoma and 30% with NSCLC share an actionable mutation in ALK or EGFR. Approximately one-half of adenocarcinoma patients have an actionable variant. Efforts should be directed toward efficiently identifying candidates for targeted agents and delivering such treatments., (© 2022 John Wiley & Sons Australia, Ltd.)

Purpose: Increasing utilization of comprehensive genomic profiling (CGP) and a growing number of targeted agents (TAs) have led to substantial improvements in outcomes among patients with cancer with actionable mutations. We sought to evaluate real-world experience with off-label TAs among Veterans who underwent CGP., Methods: The National Precision Oncology Program database and VA Corporate Data Warehouse were queried to identify patients who underwent CGP between February 2019 and December 2021 and were prescribed 1 of 73 TAs for malignancy. OncoKB annotations were used to select patients who received off-label TAs based upon CGP results. Chart abstraction was performed to review response, toxicities, and time to progression., Results: Of 18,686 patients who underwent CGP, 2,107 (11%) were prescribed a TA and 169 (0.9%) were prescribed a total of 183 regimens containing off-label TAs for variants in 31 genes. Median age was 68 years and 83% had prior systemic therapy, with 28% receiving three or more lines. Frequency of off-label TA prescriptions was highest for patients undergoing CGP for thyroid (8.6%) and breast (7.6%) cancers. Most patients harbored alterations in BRCA1/BRCA2/ATM (22.5%), ERBB2 (19.5%), and BRAF (19.5%). Among the 160 regimens prescribed > 4 weeks, 43 (27%) led to response. Median progression-free survival and overall survival were 5.3 (4.2-6.5) and 9.7 (7.5-11.9) months, respectively. Patients with OncoKB level 2/3A/3B annotations had longer median progression-free survival (5.8 [4.5-7] months v 3.7 [1.6-7.7] months; hazard ratio, 0.45; 95% CI, 0.24 to 0.82; P = .01) compared with those receiving level 4 treatments., Conclusion: Although administration of off-label TAs is infrequent after CGP, more than one quarter of treatment regimens led to response. TAs associated with level 4 annotations lead to worse outcomes than TAs bearing higher levels of evidence.

Background: Patients with advanced head and neck squamous cell carcinoma (HNSCC) associated with human papillomavirus (HPV) demonstrate favorable clinical outcomes compared to patients bearing HPV-negative HNSCC. We sought to characterize the association between HPV status and mutational profiles among patients served by the Veterans Health Administration (VHA)., Methods: We performed a retrospective analysis of all Veterans with primary HNSCC tumors who underwent next-generation sequencing (NGS) through the VHA's National Precision Oncology Program between July 2016 and February 2019. HPV status was determined by clinical pathology reports of p16 immunohistochemical staining; gene variant pathogenicity was classified using OncoKB, an online precision oncology knowledge database, and mutation frequencies were compared using Fisher's exact test., Results: A total of 79 patients met inclusion criteria, of which 48 (60.8%) had p16-positive tumors. Patients with p16-negative HNSCC were more likely to have mutations in TP53 (p < 0.0001), and a trend towards increased mutation frequency was observed within NOTCH1 (p = 0.032) and within the composite CDK/Rb pathway (p = 0.065). Mutations in KRAS, NRAS, HRAS, and FBXW7 were exclusively identified within p16-positive tumors, and a trend towards increased frequency was observed within the PI3K pathway (p = 0.051). No difference in overall mutational burden was observed between the two groups., Conclusions: In accordance with the previous studies, no clear molecular basis for improved prognosis among patients harboring HPV-positive disease has been elucidated. Though no targeted therapies are approved based upon HPV-status, current efforts to trial PI3K inhibitors and mTOR inhibitors across patients with HPV-positive disease bear genomic rationale based upon the current findings., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Aim: Globally, the incidence of lung cancer amongst women appears to be increasing. We aimed to compare the socio-epidemiological and clinical characteristics of lung cancer amongst men and women from a large cohort at a tertiary care hospital in Northern India., Methods: Records of patients diagnosed with lung cancer between January 2008 and March 2020 were reviewed. Baseline epidemiological data, clinical characteristics, histologic profiles, treatment administered, and survival were compared between males and females., Results: A total of 2054 male and 438 female patients were included in analysis. Compared to males, female patients were younger [median age, 56 vs. 60 years, P < 0.001)], less likely to be working, less educated beyond secondary level and less likely to be smokers (29.1% vs. 84.9%, P < 0.0001). No difference in baseline performance status was observed. Females were more frequently diagnosed with adenocarcinoma (54.2% vs. 30.2%, P = <0.0001), stage IV disease (70.8% vs. 63%, P = 0.001), and had higher rate of EGFR mutation (37.2% vs. 21.5%, P < 0.0001). There was no difference in the proportion of females receiving cancer-specific therapy. Multivariate Cox proportional hazards model revealed higher progression-free survival [median 9.17 vs. 7.23 months; P = 0.007] and overall survival [median 13.80 vs. 9.10 months respectively, P = 0.001] amongst females compared to males., Conclusion: Amongst a large cohort of lung cancer, females demonstrated several distinct and characteristic demographics as well as disease-related features, especially better survival outcomes., Competing Interests: None

Anemia remains a significant public health challenge, disproportionately impacting lower-income patients residing in areas of lesser healthcare resources. We sought to evaluate the accuracy of physical exam techniques to diagnose anemia among patients 5 years of age or older. A systematic review of 5 databases (MEDLINE via OVID, EMBASE, Scopus, Global Health and Global Health Archives, and WHO Global Index Medicus) was conducted. Studies that (1) compared non-invasive physical exam techniques with anemia diagnoses using standard laboratory measurements and (2) solely assessed or separately reported the diagnostic accuracy of physical exam techniques for patients 5 years or older were considered for inclusion. The diagnostic accuracies of individual and combinatorial physical exam techniques todiagnose anemia were documented. This systematic review was registered with PROSPERO. The systemic literature search yielded 6,457 unique studies after removal of duplicates. Fourteen studies were ultimately selected for inclusion. Eight studies solely assessed pregnant females, 4 solely assessed hospitalized patients, and 2 evaluated the general population. The diagnostic accuracy ranged widely for pallor assessments of conjunctivae (sensitivity: 19-97%, specificity: 65-100%), nailbed (sensitivity: 41-65%, specificity: 58-93%), and palms (sensitivity: 33-91%, specificity: 54-93%). Examining 9 or more sites leads to higher sensitivity (73.8-82.9%) and specificity (76.0-90.9%). No individual examination technique is superior to others for diagnosing anemia. Combinatorial approachs are associated with more acceptable accuracy measures, but improvements need to be balanced with time available for examination., Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01543-z., Competing Interests: Conflict of interestThe authors declare no competing interests., (© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2022.)

Objective: The majority of lung cancers are diagnosed at an advanced stage; the reasons for which are variable and unclear., Methods: Lung cancer patients were evaluated prospectively to quantify various timelines and establish reasons for delays. Timelines were defined as time intervals between symptom onset, first physician visit, first specialist visit, date of diagnosis and treatment., Results: A total 410 patients were included, majority having advanced disease. The median period for a first visit to a physician was 30 days (interquartile range [IQR] 20-90), 50 days (IQR 20-110) for referral to our centre, 23 days (IQR 14-33) to reach diagnosis, and 24 days (IQR 14.5-34) to initiate treatment. Administration ofanti-tuberculosis treatment further delayed referral to specialist centre. Treatment delays were related to performance status, disease stage and treatment type. On multivariate analysis, education and histology affected diagnosis delay and treatment delay. Treatment delay was less in those who received targeted therapy compared to chemotherapy. Various time delays did not affect the overall survival., Conclusion: Poor education status and inappropriate anti-tubercular treatment were primary factors associated with longer diagnostic delays. Creating disease awareness and high clinical suspicion are essential to overcome these lacunae in lung cancer care., (© 2022 John Wiley & Sons Ltd.)

Competing Interests: None

Spectrophotometry is a quick and reliable method for determining the composition of a variety of complex drug mixtures. Several mathematical models are available for the resolution of complex multicomponent UV spectra. UV spectrophotometric methods have the inherent capacity to resolve the interlaced spectra of complex mixtures quickly and appropriately, particularly for quantitative determination of components of mixture where several costly tools are not available. These methods also have the benefit of lower operational costs as they are operated using lesser amounts of analytical grade solvents and generate less waste. In this review, we discussed the theoretical background of different UV spectrometric methods for quantitative analysis of drug mixtures. The main focus of this review is to describe and report applications of extended Beer's law-based multicomponent analysis and to highlight the recent developments in the simultaneous determination of drug components from their complex mixtures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Poly ADP-ribose polymerase inhibitors (PARPi) are used for patients with advanced prostate cancer bearing alterations in homologous recombination repair (HRR) genes. We sought to characterize HRR gene variants and describe real-world outcomes for patients on PARPi., Methods: The US Department of Veterans Affairs' National Precision Oncology Program's database was reviewed to identify patients who underwent somatic DNA sequencing and were prescribed a PARPi before May 15, 2020. Somatic and germline variants within HRR genes were reported, and pathogenicity was reviewed via OncoKB. In patients treated with PARPi for > 4 weeks, the rate of those achieving a 30% decrease in prostate-specific antigen (PSA30) and composite progression-free survival (PFS) were compared between patients bearing pathogenic variants of BRCA2 and patients without these variants using Mann-Whitney and log-rank tests, respectively., Results: Forty-eight patients bearing 67 total HRR gene variants were prescribed PARPi for prostate cancer. Twenty-one patients (43.8%) were found to have at least one pathogenic HRR gene variant. Eight (16.6%) were referred to genetic counseling, and five (10.4%) were ultimately confirmed with germline variants. The median PFS was 4.0 months, and PSA30 was 25.6% (11 of 43) for all 43 evaluable patients. Patients with pathogenic BRCA2 variants (n = 13) had higher PSA30 (69.2% v 4.0%; P < .001) and longer PFS (7.2 v 2.8 months; P = .0291) than those without., Conclusion: In a real-world setting, heavily pretreated patients with prostate cancer and pathogenic BRCA2 variants have a significant PSA response rate and a PFS > 7 months with PARPi. This work emphasizes the importance of determining pathogenicity and origin of HRR alterations to better inform clinical treatment decisions and highlights the need for provider education and other decision support tools., Competing Interests: Vishal VashisthaEmployment: UnitedHealthcare (I)Research Funding: IBM Watson Health (Inst)Other Relationship: IBM Michael J. KelleyResearch Funding: Novartis (Inst), AstraZeneca (Inst), Bristol Myers Squibb (Inst), Regeneron (Inst), Genentech (Inst)Other Relationship: IBM (Inst) Bruce MontgomeryResearch Funding: AstraZeneca (Inst), Janssen Oncology (Inst), Clovis Oncology (Inst), Astellas Pharma (Inst), BeiGene (Inst)No other potential conflicts of interest were reported.

Objectives: A cost-effectiveness analysis comparing comprehensive genomic profiling (CGP) of 10 oncogenes, targeted gene panel testing (TGPT) of 4 oncogenes, and no tumor profiling over the lifetime for patients with metastatic lung adenocarcinoma from the Centers for Medicare and Medicaid Services' perspective was conducted., Methods: A decision analytic model used 10 000 hypothetical Medicare beneficiaries with metastatic lung adenocarcinoma to simulate outcomes associated with CGP (ALK, BRAF, EGFR, ERBB2, MET, NTRK1, NTRK2, NTRK3, RET, ROS1), TGPT (ALK, BRAF, EGFR, ROS1), and no tumor profiling (no genes tested). First-line targeted cancer-directed therapies were assigned if actionable gene variants were detected; otherwise, nontargeted cancer-directed therapies were assigned. Model inputs were derived from randomized trials (progression-free survival, adverse events), the Veterans Health Administration and Medicare (drug costs), published studies (nondrug cancer-related management costs, health state utilities), and published databases (actionable variant prevalences). Costs (2019 US$) and quality-adjusted life-years (QALYs) were discounted at 3% per year. Probabilistic sensitivity analyses used 1000 Monte Carlo simulations., Results: No tumor profiling was the least costly/person ($122 613 vs $184 063 for TGPT and $188 425 for CGP) and yielded the least QALYs/person (0.53 vs 0.73 for TGPT and 0.74 for CGP). The costs per QALY gained and corresponding 95% confidence interval were $310 735 ($278 323-$347 952) for TGPT vs no tumor profiling and $445 545 ($322 297-$572 084) for CGP vs TGPT. All probabilistic sensitivity analysis simulations for both comparisons surpassed the willingness-to-pay threshold ($150 000 per QALY gained)., Conclusion: Compared with no tumor profiling in patients with metastatic lung adenocarcinoma, tumor profiling (TGPT, CGP) improves quality-adjusted survival but is not cost-effective., (Copyright © 2021 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Indian data on treatment outcomes and survival in advanced non-small cell lung cancer (NSCLC) remain scarce., Materials and Methods: A retrospective review of 537 advanced NSCLC patients treated at a tertiary care facility in North India from January 2008 to March 2018 was done to assess treatment response and survival in terms of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS)., Results: Median age of enrolled patients was 60 years (range: 26-89 years). The majority were males (78.2%) and smokers (66.5%). Adenocarcinoma (51.2%) was the most common pathological type. Most patients had good performance status (PS) (the Eastern Cooperative Oncology Group [ECOG] 0 or 1 in 55.7%) and received conventional chemotherapy (86.6%). ORR and DCR after 3-4 months of first-line treatment were 55.2% and 71.75%, respectively (n = 223). Never smokers had better ORR as well as DCR compared to chronic smokers whereas treatment with tyrosine kinase inhibitors achieved significantly better ORR, and patients with good PS had better DCR compared to those with poor PS. Median PFS (n = 455) was 7.0 months (95% confidence interval [CI]: 3.7-14.0) and median OS was 11.7 months (95% CI: 5.5-29.9 months). Good PS and nonsmoking status were independent predictors of better PFS on multivariate analysis. For OS, good PS, nonsmoking behavior, and treatment with epidermal growth factor receptor inhibitors were independent predictors., Conclusion: In advanced NSCLC, never-smokers, and patients with good baseline ECOG have favorable treatment and survival outcomes. Treatment with targeted therapy results in better ORR and OS but did not affect PFS., Competing Interests: None

Purpose: Next-generation sequencing (NGS) gene panels are frequently completed for patients with advanced non-small-cell lung cancer (NSCLC). Patients with highly actionable gene variants have improved outcomes and reduced toxicities with the use of corresponding targeted agents. We sought to identify barriers to targeted agent use within the Veterans Health Affairs' National Precision Oncology Program (NPOP)., Methods: A retrospective evaluation of patients with NSCLC who underwent NGS multigene panels through NPOP between July 2015 and February 2019 was conducted. Patients who were assigned level 1 or 2A evidence for oncogenic gene variants by an artificial intelligence offering (IBM Watson for Genomics [WfG]) and NPOP staff were selected. Antineoplastic drug prescriptions and provider notes were reviewed. Reasons for withholding targeted treatments were categorized., Results: Of 1,749 patients with NSCLC who successfully underwent NGS gene panel testing, 112 (6.4%) patients were assigned level 1 and/or 2A evidence for available targeted treatments by WfG and NPOP staff. All highly actionable gene variants were within ALK , BRAF , EGFR , ERBB2 , MET , RET , and ROS1 . Of these, 36 (32.1%) patients were not prescribed targeted agents. The three most common reasons were (1) patient did not carry a diagnosis of metastatic disease (33.3%), (2) treating provider did not comment on the NGS results (25.0%), and (3) provider felt that patient could not tolerate therapy (19.4%). No patients were denied access to level 1 or 2A targeted drugs because of rejection of a nonformulary drug request., Conclusion: A substantial minority of patients with NSCLC bearing highly actionable gene variants are not prescribed targeted agents. Further provider- and pathologist-directed educational efforts and implementation of health informatics systems to provide real-time decision support for test ordering and interpretation are needed., Competing Interests: Vishal VashisthaEmployment: UnitedHealthcare (I)Research Funding: IBM Watson HealthOther Relationship: IBMUncompensated Relationships: IBM Watson Health Pradeep J. PoonnenHonoraria: M3, Sermo Jane L. SnowdonEmployment: IBMStock and Other Ownership Interests: IBM Dilhan WeeraratneEmployment: IBM David BrotmanEmployment: IBM Gretchen P. JacksonEmployment: IBM, Vanderbilt University Medical CenterLeadership: IBM, American Medical Informatics AssociationStock and Other Ownership Interests: IBMSpeakers' Bureau: IBMResearch Funding: IBMTravel, Accommodations, Expenses: IBM Michael J. KelleyConsulting or Advisory Role: IBMResearch Funding: Novartis, AstraZeneca, Bristol-Myers Squibb, Regeneron, GenentechOther Relationship: IBMOpen Payments Link: https://openpaymentsdata.cms.gov/physician/827136No other potential conflicts of interest were reported.

Purpose: Given the increasing number of non-small cell lung cancer (NSCLC) patients in India, a comparative analysis between patients under 40 years and those of older age at a major public referral centre would provide insight into the phenotypic patterns of this group., Methods: NSCLC patients who were accessioned within the lung cancer clinic database of the Pulmonary Medicine Department at the all India institute of medical sciences - Delhi between 2008 and 2019 were reviewed. Patients 40 years or younger and 60 years or older were selected and categorised as young and older patients, respectively. Baseline clinical characteristics, histologic profiles, treatments administered and survival outcomes were compared between both groups., Results: Following the database review, 154 young and 1,058 older patients were selected for inclusion. Clinically, young patients were more often female (26.0% versus 14.5%, p < 0.001), retained a more independent performance status (64.1% versus 45.5%; p < 0.001) and never smoked (63.7 % versus 18.8%, p < 0.001). Regarding disease profiles, young patients were more frequently diagnosed with adenocarcinoma ( p < 0.001) and 12 young patients had adenoid cystic carcinoma. Rates of stage IV disease at presentation were higher among young patients (78.0% versus 63.0%, p < 0.001). Regarding treatment, no differences in systemic therapies administered or survival were identified., Conclusion: In India, young NSCLC patients are frequently non-smokers and diagnosed with advanced disease. Despite better performance status, young patients do not share better outcomes. Efforts should be directed towards optimising intensive treatment for young patients., Competing Interests: All authors have no conflicts of interest to disclose., (© the authors; licensee ecancermedicalscience.)

Competing Interests: Competing interests: None declared.

Recent developments in precision oncology have increased the complexity of diagnostic and therapeutic decisions. Here, we broadly review the field of precision oncology and discuss common mutational drivers in non-small cell lung cancer (NSCLC) that directly relate to the diagnosis, evaluation, and treatment of patients with metastatic disease., (Copyright © 2021 The Cleveland Clinic Foundation. All Rights Reserved.)

Targeting and monitoring several acute myeloid leukemia mutations sequentially provides insights into optimal treatment plans., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article., (Copyright © 2021 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

USP5 and USP8 (Deubiquitinating enzyme) are highly overexpressed and more recognized as poor prognosis marker in various cancers. Depleting USP5 or USP8 to assess the synergism with proteasome inhibitor (Bortezomib) were measured. Furthermore, in present finding USP5 cooperates hnRNPA1 & USP8 cooperate SF2/ASF1, therefore gain in expression of either hnRNPA1 or SF2/ASF1 is sufficient to promote cell survival. On the other side, apoptosis markers were more pronounced in U87 or T98G cells devoid of either USP5 or USP8. However, apparent increase in SF2/ASF1 in absence of USP5, providing resistant factor is new. Antiapoptotic activity due to rise in SF2/ASF1 was validated after co-knock down of SF2/ASF1 in addition to USP5 induces more apoptosis comparing to individual knock down of USP5 or SF2/ASF1. This reveals SF2/ASF1 (RNA binding protein) delayed the apoptotic effect due to loss of USP5, lends ubiquitination of hnRNPA1. In presence of USP5, PI3 kinase inhibition promotes even more interaction between USP5 and hnRNPA1, thereby stabilizes hnRNPA1 in U87MG. In that way hnRNPA1 and SF2/ASF1 impart oncogenic activity. In conclusion, siRNA based strategy against USP5 is not enough to inhibit glioma, moreover targeting additionally SF2/ASF1 by knocking down USP8 is suitably more effective to deal with glioma tumour reoccurrence by indirectly targeting both SF2/ASF1 and hnRNPA1 oncogene., Competing Interests: None of the authors has no conflict of interest., (© 2020 The Author(s).)

Competing Interests: Competing interests: None declared.

Background: To support the rising need for testing and to standardize tumor DNA sequencing practices within the U.S. Department of Veterans Affairs (VA)'s Veterans Health Administration (VHA), the National Precision Oncology Program (NPOP) was launched in 2016. We sought to assess oncologists' practices, concerns, and perceptions regarding Next-Generation Sequencing (NGS) and the NPOP., Materials and Methods: Using a purposive total sampling approach, oncologists who had previously ordered NGS for at least one tumor sample through the NPOP were invited to participate in semi-structured interviews. Questions assessed the following: expectations for the NPOP, procedural requirements, applicability of testing results, and the summative utility of the NPOP. Interviews were assessed using an open coding approach. Thematic analysis was conducted to evaluate the completed codebook. Themes were defined deductively by reviewing the direct responses to interview questions as well as inductively by identifying emerging patterns of data., Results: Of the 105 medical oncologists who were invited to participate, 20 (19%) were interviewed from 19 different VA medical centers in 14 states. Five recurrent themes were observed: (1) Educational Efforts Regarding Tumor DNA Sequencing Should be Undertaken, (2) Pathology Departments Share a Critical Role in Facilitating Test Completion, (3) Tumor DNA Sequencing via NGS Serves as the Most Comprehensive Testing Modality within Precision Oncology, (4) The Availability of the NPOP Has Expanded Options for Select Patients, and (5) The Completion of Tumor DNA Sequencing through the NPOP Could Help Improve Research Efforts within VHA Oncology Practices., Conclusion: Medical oncologists believe that the availability of tumor DNA sequencing through the NPOP could potentially lead to an improvement in outcomes for veterans with metastatic solid tumors. Efforts should be directed toward improving oncologists' understanding of sequencing, strengthening collaborative relationships between oncologists and pathologists, and assessing the role of comprehensive NGS panels within the battery of precision tests., Competing Interests: In regard to potential competing interests, authors JLS, VM, DW, and GPJ are employed by IBM Watson Health. In addition, author HGS was previously employed by IBM Watson Health and author VLP is a consultant for IBM Watson Health. As mentioned, the commercial interest did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: Over the past few years, the demographic profile of lung cancer has changed. However, most reports are limited by small numbers, short follow-up period, and show an inconsistent pattern. A comprehensive evaluation of changing trends over a long period has not been done., Materials and Methods: Consecutive lung cancer patients were studied over a 10-year period from January 2008 to March 2018 at the All India Institute of Medical Sciences, New Delhi, and relevant clinical information, and survival outcomes were analyzed., Results: A total of 1862 patients were evaluated, with mean (SD) age of 59 (11.1) years, and comprising 82.9% males. Majority were smokers (76.2%) with median smoking index of 500 (interquartile range [IQR]: 300-800). Adenocarcinoma (ADC) was the most common type (34%), followed by squamous cell carcinoma (SCC - 28.6%) and small cell lung cancer (SCLC) (16.1%). Over the 10-year period, ADC increased from 9.5% to 35.9%, SCC from 25.4% to 30.6%, and non-small cell lung cancer -not otherwise specified (NSCLC-NOS) decreased from 49.2% to 21.4%. The proportion of females with lung cancer increased although smoking rates remained similar. Majority of NSCLC (95%) continued to be diagnosed at an advanced stage (3 or 4). Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements were present in 25.3% and 11.5% ADC patients, respectively. The median overall survival was 8.8 months (IQR 3.7-19) for all patients and 12.57 (IQR 6.2-28.7) months among the 1013 patients who were initiated on specific treatment (chemotherapy, targeted therapy, radiotherapy, or surgery). Never-smokers were younger, more likely to be female and educated, had a higher prevalence of ADC and EGFR/ALK mutations, and had better survival., Conclusion: Among this large cohort, our center seems to follow the global trend with increasing incidence of ADC. EGFR mutation positivity was similar to existing reports, while higher ALK positivity was detected. A characteristic phenotype of never-smokers with lung cancer was elucidated which demonstrated better survival., Competing Interests: None

A general approach to the surface control of the localization, guiding, and redirecting of volume-mode light in photonic waveguides via tailoring their interfaces (surfaces) is proposed. The approach is demonstrated for dielectric rod-type photonic crystal slabs, whose regular and defect parts are distinguished by whether the nanocylinders are covered by metal caps. Thus, the rod-array part of the structure is not changed, while the local modifications are only applied to the interfaces. The basic functionalities, i.e., localized volume wave guiding, bending, and splitting are achievable. Selective dual-mode operation is possible due to the co-existence of a defect mode and a chainlike mode in one structure.

Purpose: The Veterans Health Administration (VHA) is the largest cancer care provider in the United States, with the added challenge of serving more than twice the percentage of patients with cancer in rural areas than the national average. The VHA established the National Precision Oncology Program in 2016 to implement and standardize the practice of precision oncology across the diverse VHA system., Methods: Tumor or peripheral blood specimens from veterans with advanced solid tumors who were eligible for treatment were submitted for next-generation sequencing (NGS) at two commercial laboratories. Annotated results were generated by the laboratories and independently using IBM Watson for Genomics. Levels-of-evidence treatment recommendations were based on OncoKB criteria., Results: From July 2016 to June 2018, 3,698 samples from 72 VHA facilities were submitted for NGS testing, of which 3,182 samples (86%) were successfully sequenced. Most samples came from men with lung, prostate, and colorectal cancers. Thirty-four percent of samples were from patients who lived in a rural area. TP53 , ATM , and KRAS were among the most commonly mutated genes. Approximately 70% of samples had at least one actionable mutation, with clinical trials identified as the recommended option in more than 50%. Mutations in genes associated with a neuroendocrine prostate cancer phenotype were expressed at increased frequency among veterans than in the general population. The most frequent therapies prescribed in response to NGS testing were immune checkpoint inhibitors, EGFR kinase inhibitors, and PARP inhibitors., Conclusion: Clinical implementation of precision oncology is feasible across the VHA health care system, including rural sites. Veterans have unique occupational exposures that might inform the nature of the mutational signatures identified here. Importantly, these results underscore the importance of increasing clinical trial availability to veterans., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Pradeep J. PoonnenOther Relationship: IBMChristopher GuertinEmployment: Walmart Stock and Other Ownership Interests: WalmartVishal VashisthaOther Relationship: IBMMichael J. KelleyConsulting or Advisory Role: AstraZeneca, Eisai, IBM Japan Research Funding: Bavarian Nordic, Novartis, AstraZeneca, Bristol-Myers Squibb Other Relationship: IBMNeil L. SpectorStock and Other Ownership Interests: Eydis Bio, Bessor Pharma Research Funding: Immunolight Patents, Royalties, Other Intellectual Property: I am on a patent related to my work with the company Immunolight, and I am listed on a patent through Eydis Bio No other potential conflicts of interest were reported., (© 2019 by American Society of Clinical Oncology.)

Designing color pixels using plasmonic nanostructures and metasurfaces has become a luring area of research in recent years. Here, we experimentally demonstrated the voltage tunability of a dynamic plasmonic color filter by using an aluminum grating integrated with the nematic liquid crystal (LC). Along with a typical substrate coated with rubbed polyimide film, the aluminum grating itself serves as a molecular alignment layer to form a twisted LC cell. This hybrid structure allows electrically controlled transmission color by applying the voltage. A significant spectral tunability of such a device has been demonstrated by applying the small voltage from 0 to 4 V rms .